This proposal requests funding for a project that will establish a colony of mutant mice that manifest oral defects. Pupoid fetus (pf/pf) mice will be bred so that a decriptive study can be made of the various defects in the craniofacial region. These mice are not available in the U.S. The only breeding stock are in Glasgow and London. The oral defects include grooved tongue, cleft palate, abnormal teeth, fused oral mucosa and alterations of the stratification and keratinization patterns of the oral mucosa. Defects in the skin of the head include loss of hair and vibrissae and patent metaplasia of the epidermis. The battery of defects suggests a possible model for epidermolysis bullosa. Because the basement membrance is not maintained in the skin, the extracellular matrix components of the basement membrane will be examined by transmission electron microscopy and immunofluorescent staining. In addition, experimental tissue interactions will be monitored in order to localize the site of the defective gene expression during morphogenesis of teeth, skin and oral mucosa. Mutant mice that exhibit severe defects of the cranial and oral region are rare. This mutant offers promise as a new model to study the developmental mechanisms operating during morphogenesis of these structures. The establishment of a colony of these mice will provide an important resource for future work.